A lollipop to test for strep throat. A microfluidic device to enable signaling between cells. A kit for the remote collection of blood-based RNA (ribonucleic acid). These are among the recent innovations from Ashleigh Theberge’s chemistry lab at the University of Washington.
The Theberge Group invents bioanalytical chemistry tools to improve healthcare and advance knowledge of chemical mechanisms in the body. Many of their innovations, like the microfluidic device for cell signaling, are used in their lab. But others are for clinical research outside the lab — a growing focus of their work.
“In the early days, we were getting clinical samples — lung cells from patients with asthma, for example — and putting them into our culture platforms, but it became clear that to answer some of our questions, it would be quite complementary to do more in-depth studies in humans,” says Theberge, associate professor of chemistry in the UW College of Arts & Sciences and co-principal investigator of the lab with Erwin Berthier, UW affiliate associate professor of chemistry.
New Tools, New Questions
Theberge estimates that about half of the lab’s projects are now clinical studies, thanks to one of the team’s most impactful recent innovations: a new approach to remote sampling. She explains that clinical research often requires participants to visit a facility for blood draws, which geographically limits who can participate and how often they can be tested. Her team removed those geographic and frequency limitations by developing homeRNA, a tool for remote collection of blood that preserves cellular RNA in the blood for testing.
Why focus on collecting RNA? Simply put, RNA can provide valuable insights into genes being turned on or off as part of an immune response when an individual experiences a stressful event.
With the homeRNA kit, which can be shipped anywhere, recipients collect their sample using a push-button device developed by Tasso, Inc. that attaches to the upper arm. They then combine the sample with stabilizer fluid to preserve the RNA and ship it off to be tested. The researchers invented a stabilizer tube with integrated fluidics that simplifies the mixing of the blood sample and RNA stabilizing fluid. That has made homeRNA viable for general use.
Once homeRNA was validated in a pilot study, the lab was eager to test its potential. First they needed to identify events likely to trigger the body’s immune response to stress, then recruit study participants experiencing those stressful events. At the time, there was no shortage of stressors to choose from, with Covid-19 surging and record-breaking wildfires raging in the western US.
In separate studies, the researchers used their remote sampling technology to ask how the body alters gene expression at the onset of a Covid infection, and how the body reacts to periods of smoke exposure. “Our innovation, beyond the technology, was the intellectual thinking behind how to execute such clinical studies,” says Theberge.
I look forward to seeing tools we’ve developed be adopted broadly by the clinical research community. That will magnify the impact far beyond what a single lab can do.
For the Covid study, participants recently exposed to Covid-19 were recruited nationally through targeted ads. They provided RNA samples daily for seven days and then weekly for a short time after that. For the wildfire exposure study, participants from geographic regions prone to wildfires provided multiple RNA samples before, during, and months after wildfire smoke exposure, all using homeRNA kits shipped to them.
Prior to homeRNA, the ability to collect substantial blood-based RNA samples from far-flung study participants — repeatedly, on short notice, with a user-friendly device — had not been possible. Analyzing those RNA samples, the researchers are now learning which cellular machinery in the body is activated or suppressed in response to stressors like Covid or wildfire smoke. The knowledge may one day lead to more targeted treatments for such stress-response triggers.
The lab’s early clinical studies have led to other studies that similarly benefit from remote sampling. They are currently running a dozen clinical studies using homeRNA and other remote sampling tools, most in partnership with medical teams in the Northwest and other parts of the US. “Medical doctors have been approaching us to collaborate,” says Theberge. “It’s exciting. We’re now becoming leaders in this concept of decentralized clinical studies with very specific high content readouts.”
A Sweet Development
Concurrent with the homeRNA research, Theberge’s lab has been developing another tool for remote sampling: CandyCollect, a lollipop-inspired device that collects saliva to test for strep throat and other infections. Unlike the traditional throat swab to test for strep, CandyCollect is non-invasive and doesn’t require a clinic visit.
Sanitta Thongpang, senior research scientist in the UW Department of Chemistry, began work on CandyCollect while on the faculty of Mahidol University in Thailand, with Berthier as co-inventor. At the UW, Thongpang, Berthier, and Theberge refined the concept, designing a microfluidic channel that captures pathogens inside the lollipop device when a patient sucks on its candy-coated exterior. The collected sample is then sent to a clinic to be tested.
Besides being far more pleasant than a throat swab and more convenient for those who find clinical visits difficult, CandyCollect may also capture pathogens that a brief swab of the mouth cannot. The device also shows potential as an alternative for many invasive saliva tests that require regular or frequent sampling.
The Washington Research Foundation (WRF) recently awarded a $250,000 technology commercialization grant to support additional development of the saliva-collection device — WRF’s third grant in support of the project. The hope is that an all-in-one testing and diagnostic kit can eventually be developed, much like now-familiar rapid Covid tests. CoMotion has supported the project with a STEP grant as well.
If that sounds like a bold goal, Theberge’s research team is up for the challenge.
“When I reflect on our work over the past two years, it’s amazing how much our team has accomplished,” she says of the lab’s many projects. “I look forward to seeing tools we’ve developed be adopted broadly by the clinical research community. That will magnify the impact far beyond what a single lab can do.”