Molecular diagnostic company Wave 80 Biosciences has received Phase I Small Business Innovation Research funding from the National Institutes of Health to develop rapid sample prep to support chlamydia testing in low-resource settings.
The two-year grant, administered by the National Institute of Allergy and Infectious Diseases, provides $300,000 in the first year to develop solid phase RNA extraction, filtering, lysis, and binding to a porous polymer monolith, in order to extract nucleic acids from vaginal swabs or urine.
The method will be an improvement over currently available sample prep methods because it will not require centrifugation, and can be run in an inexpensive, disposable cartridge, according to the project information.
Amy Droitcour, vice president of engineering at the company and project leader on this grant, told PCR Insider this sample prep cartridge could then be used at the point of care to diagnose and treat patients in a single visit to the clinic. "We plan to use it either fully integrated with a downstream nucleic acid test, or in a two-part model, where someone could buy just the sample prep and then use that output with another nucleic acid test," she said.
The sample prep cartridge will be based on Wave 80's slit capillary array fluidic actuator chips, or SCAFA. This proprietary chip design uses electro-osmosis to transport the fluid phase relative to a stationary solid phase, somewhat the opposite, conceptually, of electrophoresis, said Droitcour. Electro-osmosis is associated with submicron-scale charge double-layers at the fluid-solid interface. The SCAFAS are made by etching 5-by-100-micron slits in silicon, and then putting "thin films on the surface in order to make a passivation layer that we've optimized to make an electric double layer, which gives us the power transduction from electrical to fluid power," she said. Lysis, extraction, washing, and elution steps are all driven by pressure from the SCAFAs, according to Droitcour. "With those methods we've shown recovery rates that are comparable to the best centrifugation-based methods in HIV with blood samples," she added.
The company previously received SBIR funding to develop the downstream end of the chlamydia test. Droitcour explained they wrote the grant for the downstream testing first because "at that time we thought that the [Bill and Melinda] Gates Foundation was going to be coming out with this great, low-cost, versatile, point-of-care-compatible, nucleic acid test sample prep system. But it didn't seem to materialize, so we decided to start working on it for chlamydia and gonorrhea." Droitcour said they got promising preliminary results from their method, and so submitted the second grant based on those.
Chlamydia is a major health concern in the US. It is one of the most common STDs, with over 3 million new infections every year. Men typically experience symptoms and initiate antibiotic treatment, but the majority of cases in women are asymptomatic. Untreated, this can cause pelvic inflammatory disease or even irreversible infertility, and can be passed to newborns leading to conjunctivitis and blindness.
Droitcour pointed out that the US Centers for Disease Control and Prevention changed their guidelines for chlamydia in 2010 and now mandates testing for women under age 25, older women with certain risk factors, and all pregnant women. Regardless of the new guidelines, more than half of women are not getting routinely screened, said Droitcour. "Part of the reason is there are no really effective rapid tests for chlamydia. There are actually a few papers out [with titles] like 'Alarmingly poor performance in Chlamydia point-of-care testing,'" she said.
Chlamydia is also a disease that disproportionately affects minority and low income populations. "These people are often going to small hospitals or community health centers that don't have a clinical lab infrastructure in house, or the resources of larger hospitals," Droitcour said. "They have to take a sample, send it out, the turnaround time is often a week or so before they get the results back in, and a lot of these clinics don't have the resources to track down the people with the results they get. It's called loss-to-follow-up, so people aren't finding out their results and getting treated from their screening."
Wave 80 plans to develop its chlamydia test for the US market. The full assay would require an instrument for detection, which Droitcour said is basically the same hardware the company currently uses for its HIV product, called Eoscape. This product was recently headed for full-scale clinical trials, as reported in PCR Insider. However, Droitcour said, "We saw some results from the long term storage of some of the reagents that gave us some concern, so we're reengineering some aspects of the assay to ensure that the cartridges are going to have the stability properties that we need for high disease burden countries."
The company is considering various options for commercializing the chlamydia sample prep and diagnostic, including licensing assays or developing its own product, Droitcour said. "At this point I don't think we can project the actual cost of the chlamydia project. However, since we first moved into nucleic acid testing back in 2007 we've been very focused on low cost for both consumables and instrumentation, and we'll certainly stay true to that for chlamydia," she said.