Doctor using a smartphone

Photo by Daniel Sone

Scientists say a smartphone-based system could bring rapid, accurate molecular diagnosis of cancers and other diseases to locations lacking the latest medical technology.

In PNAS, the group explained how the digital diffraction diagnosis (D3) system collects detailed microscopic images for digital analysis of the molecular composition of cells and tissues.

In pilot experiments, the system enabled accurate diagnoses of lymphoma and cervical cancer.

“The emerging genomic and biological data for various cancers, which can be essential to choosing the most appropriate therapy, supports the need for molecular profiling strategies that are more accessible to providers, clinical investigators, and patients,” said study author Cesar Castro, MD, of Massachusetts General Hospital in Boston.

“And we believe the platform we have developed provides essential features at an extraordinarily low cost.”

The D3 system features an imaging module with a battery-powered LED light clipped onto a standard smartphone that records high-resolution imaging data with its camera.

With a greater field of view than traditional microscopy, the D3 system is capable of recording data on more than 100,000 cells from a blood or tissue sample in a single image. The data can then be transmitted for analysis to a remote graphic-processing server via a secure, encrypted cloud service, and the results returned to the point of care.

For molecular analysis of tumors, a sample of blood or tissue is labeled with microbeads that bind to known cancer-related molecules and loaded into the D3 imaging module.

After the image is recorded and data transmitted to the server, the presence of specific molecules is detected by analyzing the diffraction patterns generated by the microbeads. The use of variously sized or coated beads may offer unique diffraction signatures to facilitate detection.

A numerical algorithm the researchers developed can distinguish cells from beads and analyze as much as 10 MB of data in less than nine hundredths of a second.

In a pilot test with cancer cell lines, the D3 system detected the presence of tumor proteins with an accuracy matching that of the current gold standard for molecular profiling. And the system’s larger field of view enabled simultaneous analysis of more than 100,000 cells at a time.

The researchers also conducted analyses of cervical biopsy samples from 25 women with abnormal PAP smears—samples collected along with those used for clinical diagnosis—using microbeads tagged with antibodies against 3 published markers of cervical cancer.

Based on the number of antibody-tagged microbeads binding to cells, D3 analysis promptly and reliably categorized biopsy samples as high-risk, low-risk, or benign. Results matched those of conventional pathologic analysis.

In addition, D3 analysis of fine-needle lymph node biopsy samples was accurately able to differentiate 4 patients whose lymphoma diagnosis was confirmed by conventional pathology from another 4 patients with benign lymph node enlargement.

Along with protein analyses, the D3 system was enhanced to successfully detect DNA—in this instance, from human papilloma virus—with great sensitivity.

In all of these tests, results were available in under an hour and at a cost of $1.80 per assay, a price that would be expected to drop with further refinement of the D3 system.

“We expect that the D3 platform will enhance the breadth and depth of cancer screening in a way that is feasible and sustainable for resource limited-settings,” said Ralph Weissleder, MD, PhD, also of Massachusetts General Hospital.

“By taking advantage of the increased penetration of mobile phone technology worldwide, the system should allow the prompt triaging of suspicious or high-risk cases that could help to offset delays caused by limited pathology services in those regions and reduce the need for patients to return for follow-up care, which is often challenging for them.”

The researchers’ next steps are to investigate D3’s ability to analyze protein and DNA markers of other disease catalysts, integrate the software with larger databases, and conduct clinical studies in settings such as care-delivery sites in developing countries or rural areas.

Massachusetts General Hospital has filed a patent application covering the D3 technology.

System can diagnose lymphoma, other diseases