CANCER could soon be self-diagnosed with a simple urine test.
Researchers have developed a new nanoparticle sensor that works similar to a pregnancy test to quickly and inexpensively detect the deadly disease.
The sensors could even be used to distinguish different types of cancer and assess whether tumors recur after treatment.
The nanoparticles are intended to detect tumors and release DNA sequences that can then be detected in the urine.
Analysis of these DNA “barcodes” could reveal details about a patient’s tumor.
Initial tests in mice showed that sensors could be used to detect the activity of five different enzymes expressed in tumors, and further human clinical trials are in preparation.
To make their test as cost-effective and easily accessible as possible, engineers at Massachusetts Institute of Technology (MIT) in the US designed it to be carried out on a paper strip – similar to a pregnancy or lateral flow Covid test. Test.
dr Sangeeta Bhatia, a bioengineer and professor at MIT’s Institute for Medical Engineering and Science and Electrical Engineering and Computer Science (EECS), said, “We try to innovate in the context of bringing technology to people with low and medium resources.”
“Putting that diagnosis on paper is part of our goal to democratize diagnostics and develop cost-effective technologies that can give you a quick answer at the point-of-care.”
For several years, Dr. Bhatia’s lab “synthetic biomarkers” that could be used to diagnose cancer.
This latest project builds on previous work on detecting biomarkers of the disease, such as proteins that circulate around tumor cells in patients’ blood samples.
But these naturally occurring biomarkers are so rare, especially in the early stages of cancer, that they are almost impossible to find.
However, synthetic biomarkers can be used to amplify these small changes that occur in small tumors.
In her previous work, Dr. Bhatia has developed nanoparticles that can detect the activity of enzymes called ‘proteases’ that help cancer cells migrate from their original site or to establish a new site.
These nanoparticles are coated with peptides that are cleaved by various proteases. Once these peptides enter the bloodstream, they can be concentrated and more easily detected in a urine sample.
The original peptide biomarkers were designed to be detected using a mass spectrometer based on small variations in their masses – however, this type of equipment is unlikely to be available in less resourced environments.
Instead, the researchers developed sensors that are easier and cheaper to analyze using DNA barcodes read with a specially developed technology called “CRISPR”.
The research team also had to apply a chemical modification to protect the circulating DNA reporter barcodes from being broken down in the blood during travel.
Each DNA barcode is attached to a nanoparticle via a linker that can be cleaved by a specific protease.
When this protease is present, the DNA molecule is released and allowed to circulate freely, eventually ending up in the urine.
Once the sensors are excreted in the urine, the sample can be analyzed using a paper strip that recognizes a reporter activated by a CRISPR enzyme.
When a specific DNA barcode is present in the sample, Cas12a amplifies the signal so that it shows up as a dark band on a paper test.
The particles can be engineered to carry many different DNA barcodes, each recognizing a different type of protease activity, allowing for ‘multiplexed’ recognition.
Using more sensors increases both sensitivity and specificity, making it easier for the test to discriminate between tumor types.
In recent tests using mice, the researchers showed that a panel of five DNA barcodes can accurately distinguish tumors that first arose in the lungs from tumors formed by colorectal cancer cells that had metastasized to the lungs.
Liangliang Hao, a former MIT research scientist who is now an assistant professor of biomedical engineering at Boston University and the study’s lead author, said, “Our goal here is to build up disease signatures and see if we can use these barcode panels.” only to screen for a disease, but also to classify a disease or distinguish between different types of cancer.”
For future use in humans, the researchers anticipate that the variety of patients’ tumors may require them to use more than five barcodes, as they did with the mice.
To this end, the researchers, together with scientists from the Broad Institute of MIT and Harvard, have developed a microfluidic chip that can read up to 46 different barcodes from just one sample.
This type of test could be used not only to detect cancer, but also to measure how well a patient’s tumor is responding to treatment and whether it has come back after treatment.
The researchers are now working on the further development of the particles with the aim of testing them on humans.