Simple Paper Test Analyses Urine Samples for Early Cancer Diagnosis

Engineers at Massachusetts Institute of Technology (MIT, Cambridge, MA, USA) have developed an innovative nanoparticle sensor that could facilitate early cancer diagnosis through a simple urine test. These sensors can identify various cancerous proteins and may also help differentiate tumor types or gauge treatment response. When the nanoparticles encounter a tumor, they release short DNA sequences that appear in the urine. Examining these DNA "barcodes" can expose specific characteristics of a patient's tumor. The test is designed to work with a paper strip, which could make it cost-effective and widely accessible.

The researchers employed two kinds of nanoparticles for their study: an FDA-approved polymer-based particle for human use and a "nanobody" - an antibody fragment designed to accumulate at the tumor site. Once the sensors are secreted in the urine, the sample is analyzed using a paper strip that recognizes a reporter activated by the CRISPR enzyme Cas12a. If a specific DNA barcode is present in the sample, Cas12a amplifies the signal, resulting in a visible dark strip on the paper test. These particles can be engineered to carry multiple DNA barcodes for detecting different protease activities, enabling "multiplexed" sensing. Additionally, using more sensors enhances sensitivity and specificity, allowing the test to differentiate between tumor types more effectively.

In mouse trials, the researchers demonstrated that a set of five DNA barcodes could accurately differentiate lung tumors from colorectal cancer metastases in the lungs. Their method could also scale up to identify at least 46 distinct DNA barcodes in a single sample using a microfluidic device. Given the significant variability in human tumors, more than five barcodes may be required for human use. To address this, the researchers have developed a microfluidic chip capable of reading up to 46 DNA barcodes from a single sample. This testing approach could be employed not only for cancer detection but also for monitoring treatment response and recurrence. The researchers are now focused on refining the nanoparticles and preparing them for human trials.

“We are trying to innovate in a context of making technology available to low- and middle-resource settings. Putting this diagnostic on paper is part of our goal of democratizing diagnostics and creating inexpensive technologies that can give you a fast answer at the point of care,” said Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

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