NEW YORK (360Dx) – With an eye toward low-resource settings, a research team from the University of Illinois at Urbana-Champaign has developed smartphone-enabled diagnostic technology that can perform many of the same testing currently performed with laboratory-based immunoassays.
Describing their work recently in a study published in Lab on a Chip, the scientists said the technology, which costs about $550, could "serve as a platform for rapid, simple translation of existing commercially available biosensing assays to a [point-of-care] setting."
Commercialization of the technology, dubbed the spectral transmission-reflectance-intensity (TRI) Analyzer, for some applications that don't require regulatory approvals could come as soon as in a year, said Brian Cunningham, the principal investigator on the project, and a professor of electrical and computer engineering at the University of Illinois at Urbana-Champaign, where he is also the director of the Micro and Nanotechnology Lab.
The system comprises the TRI Analyzer and a cartridge. According to Cunningham, the analyzer acts essentially as a cradle that attaches to a smartphone, turning it "into a relatively sensitive and high-resolution spectrophotometer." Meantime, the cartridge contains a series of small chambers that can be scanned through the analyzer.
The cartridge runs "many measurements in series, one after another, kind of in the same way that you would scan a magnetic strip on a credit card through a credit card reader," Cunningham said in an interview.
As the cartridge runs through the cradle, the phone's camera, acting as a spectrometer, records video and measures the color spectrum or the light emission spectrum of the liquid in the chambers. An app developed to run on the phone while the analyzer is being used, measures the data, does an analysis, reports the results to a user, and then communicates it to a cloud database.
To validate their technology, Cunningham and his team used the system with two commercially available assays — one to detect fetal fibronectin, a glycoprotein with a high negative predictive value for spontaneous preterm birth; the other, a phenylketonuria test used to indirectly determine whether a newborn has an enzyme required for normal growth and development — and compared the results with a benchtop 96-well plate reader.
For the commercially available fetal fibronectin test, they found that the TRI performed comparably with the microplate reader. "Similar limits of detection were observed between the 96-well microplate reader and spectral TRI analyzer, both well under the minimum assay detection range (25 ng mL-1), with the lowest discernable assay concentration being 37.0 and 12.3 ng mL-1 respectively," they said, adding that after Bland-Altman analysis was performed on the two platforms, all data were shown to be "well within the 95 percent confidence intervals."
Similarly, using a commercially available PKU test, they found that the fluorescence spectra generated by the TRI analyzer "resulted in a clear dose-response curve with a comparable limit of detection to that of the commercially available plate reader." They noted, however, that they saw saturation of their signal at higher analyte concentrations, which suggests that the TRI analyzer may have a lower dynamic range than the microplate reader.
Cunningham said the TRI Analyzer is suitable for tests that use colored liquids and light-emitting liquids, a method commonly used in immunoassays. The analyzer would use extant tests already used with lab-based systems. "All the tests that are performed in microtiter plates that have an antibody incorporated within the microtiter plate can have that same antibody incorporated into a cartridge like ours," Cunningham said.
What it would not be suitable for are tests that measure chemical compounds directly from a sample, for example, a mass spectrometry-based test.
"What we were setting out to do was developing methods to make laboratory-based tests that are performed in diagnostic labs of hospitals, or … laboratory facilities to make them inexpensive, easier, and more accessible, so that people could perform those kinds of tests in person, at the point of use or point of care," he said.
He envisions the TRI analyzer being used in settings such as health clinics and pharmacies "where a test like this could be performed by a technician very simply." Additionally, he said that it would have use with home health aides taking care of patients, in nursing homes, and in ambulances.
But specifically, he and his colleagues developed their technology with an eye at low-resource settings, including developing nations and rural communities, and the researchers are looking to collaborate with parties "who are interested in this who have other applications in mind," Cunningham said.
He added that there has been interest among some commercial entities in the TRI technology. He declined to name them, but said they are potentially looking at using or developing the analyzer for applications ranging from food safety to environmental health, water measurement, animal health, and human health.
As a diagnostic tool for humans, the device would require the thumbs-up from the US Food and Drug Administration, which the researchers are leaving to potential collaborators to pursue, Cunningham said. For now, the prototype works well enough that it could feasibly be commercialized within a year for purposes that don't require FDA clearance or approval.
For research-related applications, Cunningham said that his team remains primarily interested in assays used for maternal and child health, "since those are the ones that are important to developing parts of the world."
They also are collaborating on a flu panel and are interested in TRI tests for Zika, dengue, and chikungunya.
For an ELISA assay, the time to result on the platform currently takes "a couple of hours," and reducing it would entail work on the actual chemistry of the test, which Cunningham and his team are not doing. "We have other collaborators working on more rapid ELISA methods," he said.
Even with its current time to result, he said, the TRI system could be used in settings where rapid results are necessary. "Many tests [still] have the samples sent away to a remote lab," he noted.
If successfully commercialized, it would join a growing number of technologies in the mHealth arena. Other firms that have or are developing diagnostic tools that can be used with smartphones include Rennova Health and Certainty Health, Brigham and Women's Hospital, and Roche.
One key draw of the TRI Analyzer, the researchers said, is its cost — $550 in components. "Many previous proof-of-concept demonstrations have focused on a single usage case, which significantly decreases the cost effectiveness of any diagnostic device," they wrote in the study. "The broad applicability of our device provides a necessary linkage between this previous work and the future possibility of truly portable IVD devices."
Cunningham added that industry has told him that in the manufacturing process, as volumes increase, costs decrease "and so it seems likely the costs in the manufacturing mode could be between $100 and $200, almost to the point where companies we've talked to describe it as wanting to give away the hardware, and then to sell the test kits as a way to earn money."
Moving forward, however, refinements would need to be made to the system, including making the interface for the software more streamlined and user-friendly. "And then … we're also developing approaches to incorporate the reagents of the assay into the cartridge itself, so that the entire test can be streamlined from the initial sample, all the sample processing, all the way to result," Cunningham said.