By Deborah Borfitz
November 11, 2020 | Physicians could use a diagnostic device to aid clinical decision-making for patients with cancer and chronic diseases at the point of care (POC)—be that in the home, doctor’s office, or hospital emergency department. Most prototype systems never make it to market because they fail to work well with unprocessed patient samples and their developers run out of money trying to develop a commercially viable, regulatory-grade product, says Leyla Soleymani, a biomedical engineer and Canada Research Chair in miniaturized biomedical devices at McMaster University.
Researchers at McMaster and Brock universities have overcome the first hurdle by developing a handheld device to measure prostate specific antigen (PSA) and, potentially, clinical markers of other types of cancers and conditions or their symptomatology. The prototype is designed to read diagnostic signals from a drop of blood, Soleymani says.
The electrochemical bio‐barcode assay has three components—a solution vial that produces all the needed reagents, a signal-generating chip and a barcode reader. Most of the innovation lies in the solution vial, where a DNA machine (aka DNA-protein conjugates) recognizes the biomarker of interest and generates a specific barcode that gets detected electrically on the chip, she explains. The reader, similar to a UBS stick, can be plugged into a smartphone, tablet or computer.
Patients self-administering the test from home would have only to give themselves a finger prick to obtain a drop of blood, mix it with the reactive liquid, place the vial onto a strip and insert it into the reader, says Soleymani. Within minutes, the device can measure how much cancer is in the body based on blood PSA level. The proof-of-concept work was recently described in Angewandte Chemie (DOI: 10.1002/ange.202009664)
Feng Li, an associate professor of chemistry at Brock University and co-leader of the research collaboration, has been developing DNA machines for many years using lab-based instruments to read fluorescent signals, Soleymani says. To make the technology compatible with POC diagnostics required reengineering the molecular barcodes to make them reliably readable by biosensors used in glucose monitors.
Diagnostic Yield
PSA is somewhat of a controversial biomarker for diagnostics, due largely to its lack of specificity, but it was a good starting point because it has been well-studied, is commercially available with reliable suppliers, and collaborators had access to samples from prostate cancer patients, says Soleymani. It is also a good marker for monitoring prostate cancer.
The research team plans to raise funds to create a multiplex assay that can detect up to 10 other biomarkers so the device can more accurately diagnose disease, including its stage and type, as well as predict how well a particular patient will respond to therapy, she adds. The goal is to combine relevant, disease- or symptom-specific biomarkers to achieve high diagnostic sensitivity and specificity, and Soleymani says she is talking to commercial entities and clinicians daily for guidance on creating relevant panels.
Depending on the panel and the disease, the device might get used in a physician’s office to diagnose or monitor patients or at home to monitor for recurrence biomarkers, she continues. “This by no means replaces care by physicians. It just generates more data points, ever day or every week, so they can make better decisions.”
Results would identify red flags for when patients might need to see the doctor between scheduled appointments or have their medications adjusted, says Soleymani. Ultimately, assuming the system gets integrated into the bigger workflow of the healthcare system, assay readouts could automatically be sent to the cloud and routed to patients’ physician or electronic medical record.
Clinical Studies
Regulatory approval of the electrochemical bio‐barcode assay will necessitate head-to-head comparisons of its clinical sensitivity and specificity with laboratory-scale instruments on large numbers of clinical samples, Soleymani notes. Presumably, agreement in the 90%-plus range will be the targets to hit.
To date, the device has been used on plasma samples from 10 patients that were “spiked” with PSA, she says. The first controlled clinical trial is expected to begin in the next few months and will include fully unprocessed clinical samples from patients with and without prostate cancer.
The journey to commercialization will likely take another two to five years but, when it happens, it’s “going to be a big deal,” she adds. Truly patient-centered decision-making requires more frequent POC testing so baselines and biomarker trends don’t default to averages across entire populations—and individuals aren’t needlessly panicked if their numbers spike for a moment in time or an inconsequential reason.