NEW YORK – Under a new National Institutes of Health grant issued last month, researchers at the University of California, Los Angeles aim to apply a technology called "electrochemical liquid biopsy" (eLB) to predict high-risk pregnancies.
Awarded $600,000 for the first year of the grant, the researchers hope to eventually develop a point-of-care assay that can detect the risk of conditions during pregnancy before their symptoms occur, which they believe might allow for timely interventions and eliminate placenta-related disorders.
"The idea is that we want to diagnose something before it happens, so that you can predict it, which would lend itself to closer monitoring of pregnancy," Sherin Devaskar, a pediatric professor at UCLA and co-project leader, explained.
Devaskar said that several risk factors that develop during pregnancy can impact both the patient's and baby's health over time. Conditions such as gestational diabetes and intrauterine growth restriction can lead to serious health issues if not diagnosed and treated properly.
While clinicians can use a variety of tests — including ultrasound, MRI, and glucose testing — to diagnose these issues, Devaskar noted that they do not really predict the conditions and are also often invasive, "since you either need to draw a blood sample or put a pregnant woman through imaging."
Devaskar and her team therefore believe that developing a non-invasive biosensor that can quickly detect RNAs and proteins in urine can accurately assess longitudinal health in a patient's placenta during pregnancy. The group will work with a biobank at UCLA created by Devaskar by testing anonymized urine samples of patients with different conditions that lead to high-risk pregnancies.
As part of the five-year project, Devaskar's group will develop a customized eLB device to measure multiple transcripts and proteins in urine collected longitudinally during normal pregnancies. The team has begun testing validated biomarkers linked to the different health conditions, and also plans to search for new biomarkers potentially associated with the conditions.
The group will also examine the biosensor's ability to detect transcript and protein differences between normal and high-risk pregnancies, as part of preparing for future POC testing in achieving real-time noninvasive and rapid monitoring of placentas.
The group will validate the tool by comparing the UCLA biobank urinary samples to paired blood samples, placental gene expression, and clinical outcomes.
According to Devaskar, the original technology was co-invented at UCLA by the project's co-leader and associate professor Fang Wei and professor Wei Liao, who launched a startup called EZLife Bio in 2016 to commercialize the technology for cancer diagnostic applications. Called EFIRM — short for electric field-inducing release and measurement method — the technology uses a conducting polymer-based electrochemical chip with gold electrodes and employs an electrical field to detect biomarkers in liquid samples.
Learning that Wei's lab was using EFIRM in lung cancer research trials, Devaskar wanted to see if her team could use the biosensor technology to potentially identify relevant biomarkers for a variety of different high-risk conditions during pregnancy.
"By using an electrochemical field, we can hopefully detect target biomarkers," Devaskar explained. "While the tool has been used in other fields, particularly in cancers, this seems to be the first time that researchers are doing it to predict high-risk pregnancies."
Instead of using standard PCR or sequencing methods, Devaskar's team will apply eLB to detect specific biomarkers because the group can directly measure urine samples without requiring any pretreatment steps, which she believes will allow the technology to work in point-of-care modes. Devaskar highlighted that this characteristic will be crucial for long-term monitoring of biomarkers from patients during pregnancy.
Devaskar also believes that eLB also stands out from standard tools because it is non-invasive, requires a small sample volume (less than 40 μl per assay), a shorter run time (less than two hours), and could easily be made into a miniaturized device.
While expecting to work with larger sample cohorts and partner with academic collaborators in future studies, Devaskar said that the technology is nascent and not far enough along to transition into a potential assay for the NIPT space.
"While this grant is not geared toward enrolling patients, we want to test [electrochemical liquid biopsy] and ensure that [the technology] really lives up what we expect it to do, so that we can deploy it [as an assay] for diagnostic applications," Devaskar said.
Devaskar highlighted that her team wants to diagnose cases of preeclampsia — high blood pressure and hypertension — before it leads to permanent damage to a baby during pregnancy. Because the condition compromises the blood flow to the baby in the placenta, clinicians usually observe smaller birth sizes, followed by irregular growth and obesity issues as the child grows up.
"If we can break that cycle and have healthier mothers and babies, they will end up being healthier adults and minimize the chance of diabetic and high blood pressure-related problems," Devaskar said.