NEW YORK – University of Houston spinout Luminostics is developing a luminescent nanoparticle lateral flow platform that it believes will achieve far better performance than current commercial tests using similar technology.
The firm's diagnostic platform in development, called Clip, uses lateral flow as the basis of its design, but its photoluminescent phosphor nanoparticle materials contribute most to the platform's potential for future deployment in testing at home, in doctors' offices, and in global health clinics, Bala Raja, the company's cofounder, said in an interview.
Current lateral flow immunoassays take sophisticated technology and convert it to a test strip that almost anyone can operate. However, most lateral flow platforms are not sensitive enough for broad use in clinical testing. Higher sensitivity lateral flow tests are available, Raja noted, but the use of fluorescently labeled antibodies that enable higher sensitivity also adds to system costs that may be affordable for doctors' offices but not for use at home.
"The simplest way to describe what we have done with our system is to say that we have turbocharged the lateral flow format, while maintaining a low cost and small form factor that will enable it to be used over-the-counter for testing," Raja said.
Instead of using traditional fluorescence labels, the system's phosphor nanoparticles and time-gated imaging approach enables its use with a standard smartphone instead of a new reader, contributing to affordability. The system uses the camera flash to briefly excite its phosphor nanoparticles, and it uses the camera lens to capture images of phosphor luminescence associated with the presence of a target analyte.
The approach is enabled, according to Raja, by its phosphor nanoparticles, which exhibit a property called persistent luminescence whereby they glow for an extended duration, similar to glow-in-the-dark materials.
"The main reason all of this is cheap is because of an imaging technique called time-gating," Raja said. "That is connected to being able to charge up the particles and turn off the excitation source and still have the particles glow bright. It enables us to avoid using an expensive optical filter or an expensive light source."
With users deploying their own mobile phones for yet another task, the platform may one day be made available at prices that are competitive with both over-the-counter and professional-use lateral flow tests, Raja said.
The near-term applications within its sights are similar to those for which many diagnostics developers are looking to provide point-of-care tests. While these applications include assays that would enable testing for respiratory infections, the firm has gathered most of its platform validation data in testing for sexually transmitted diseases.
Barbara Van Der Pol, president of the American STD Association and the director of a diagnostic lab at the University of Alabama at Birmingham School of Medicine, said in an interview that "reliable, rapid, and affordable STI tests can be used in patient care settings, and potentially by users as over-the-counter products."
These tests have the potential to make STI testing "a routine health-maintenance behavior for all sexually active people," she said, adding that women, in particular, can begin to take control of their own sexual health "in the same way that we monitor ovulation and pregnancy, or manage vaginal yeast infections."
With the Luminostics test, Ven Der Pol said, managing sexual health could become a reality for many sexually active adults by using an inexpensive adapter that allows a smart phone to provide the necessary technology to perform and interpret the test. "This will be an important leap forward in the public health effort to control STIs and reduce the burden of disease at the population level," she added.
Raja said he believes that the firm's test for chlamydia could be available with 510(k) clearance and CE marking in about two years. However, the timelines for launching a first product depend heavily on the firm being able to engage with strategic partners and obtain adequate funding, complete product development, and run clinical trials. The types of tests it deploys first are also likely to depend on the interests of potential partners, he noted.
To support its commercial initiatives, the San Jose, California-based firm is seeking an undisclosed amount of funding and looking to identify "partners that want to leverage the advantages of our platform to either improve an existing product line or to create a new product line," Raja said.
The firm has been funded by the National Institutes of Health and venture capital investors, including Y Combinator and Khosla Ventures. Alexander Morgan, a principal at Khosla Ventures, said in an interview that the venture capital firm sees chlamydia as a major neglected public health issue that affects men but particularly women, "substantially contributing to infertility and ectopic pregnancies."
He said Khosla Ventures is "very supportive of efforts to combat this" and noted that Luminostics has recently demonstrated the diagnostic accuracy of its platform in a high-risk population human study.
The point-of-care test developer has published three peer-reviewed papers — one in Analytical Chemistry in 2014, a second in Lab on a Chip in 2017, and a third in PLoS One earlier this month — that describe the development and operation of the platform. In the Analytical Chemistry study, the group demonstrated detection of human chorionic gonadotropin using strontium aluminate nanoparticles.
Raja and his colleagues are putting the finishing touches on a study that reflects recent development activities.
In a recent clinical trial, to which Morgan alluded, investigators evaluated the sensitivity and specificity of the Clip platform while testing for chlamydia in patients in Indonesia. The group tested 437 patients, of which 52 were positive and 385 were negative, using either the Cepheid GeneXpert or Hologic Aptima nucleic acid tests for chlamydia. The Luminostics platform had a positive percent agreement of 89 and negative percent agreement of 99 with the comparator tests, Raja said. Further, when compared to the sensitivity of visually read lateral flow assays, the phosphor luminescence lateral flow platform is showing performance levels that are one hundred times more sensitive, he added.
For a diagnostic tests sold over the counter and used in the home, the company envisions participating in three testing categories — infectious disease testing and the guidance of treatment; endocrinology; and testing and monitoring of chronic diseases, including monitoring post-surgery and tracking cancer recurrence, cardiovascular disease, and autoimmune conditions.
"Our vision is to combine at-home diagnostics with an immediate telehealth consult," Raja said. "With infectious disease tests, you can't just tell someone that they're positive and leave them hanging. You want to also link them to care and get them a prescription or connect them to a doctor for a video call."
The development of the multiplex diagnostic test using lateral flow may be particularly timely, according to Brendan O'Farrell, president of Carlsbad, California-based DCN Diagnostics, a contract development firm for rapid tests. In recent years, there's been "a huge shift in market demand for lateral flow technology, both from a technical and an application perspective," O'Farrell said. "Specifications are trending more towards very high sensitivity, speed, quantification, multiplexing, and utilization by untrained users in a wide variety of environments, including consumer spaces."
He added that Luminostics' "higher sensitivity performance in certain lateral flow applications" may enable "the deployment and digital interpretation of assays in a variety of environments where fast, laboratory-free result generation is key."
With increasing recognition of the importance of rapid testing at the point of care for sexual health applications, competitors are developing tests in anticipation of future market entry.
In August, Ghent, Belgium-based MyCartis announced it was spinning off its point-of-care business into a separate company called Antelope Dx to focus on developing and commercializing a point-of-care multiplex test for chlamydia and gonorrhea, among other conditions. During the same month, the US Food and Drug Administration granted a first of its kind 510(k) clearance permitting sale of Binx Health's point-of-care test to detect chlamydia and gonorrhea.