Simple urine test that leads to cancer being self-diagnosed could be on the way
A simple urine test has been developed so that cancer may one day be self-diagnosed.
American researchers have created a new nanoparticle sensor to quickly and cheaply diagnose cancer in a test designed to be affordable and accessible to all.
The sensors, which work much the same as pregnancy tests, can detect cancerous proteins and could even be used to distinguish between different types of cancer and evaluate whether tumours recur after treatment. The nanoparticles are designed to search out tumours and emit DNA sequences when they do, which are then detectable in urine.
Analysis of this DNA could reveal details of a patient's tumour. Initial tests in mice demonstrated sensors could be used to detect the activity of five different enzymes expressed in tumours, and further clinical trials in humans are in the offing.
Engineers from the Massachusetts Institute of Technology (MIT) designed the nanoparticle sensor which can detect various cancerous proteins.
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The nanoparticles are designed so that, once they encounter a tumour, they shed short sequences of DNA which are later excreted in the urine.
Analysing these DNA 'barcodes' from the urine can reveal distinguishing features of a patient's tumours. The MIT research team, in aiming to make their test as cost-efficient and easily accessible as possible, designed their test to be performed on a strip of paper - similar to a pregnancy test or lateral-flow Covid test.
Dr Sangeeta Bhatia, a biological engineer and a professor at MIT’s Institute for Medical Engineering and Science and Electrical Engineering and Computer Science (EECS), explained: "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 democratising diagnostics and creating inexpensive technologies that can give you a fast answer at the point of care."
For some years now, Dr Bhatia's lab has been developing 'synthetic biomarkers' that could be used to diagnose cancer. This latest project builds on previous work in detecting the biomarkers of cancer, such as proteins circulating around tumour cells in patients' blood samples.
But these naturally occurring biomarkers are so rare - especially during the early stages of cancer - that they're nearly impossible to find. However, synthetic biomarkers can be used to amplify these small-scale changes occurring within small tumours.
In her previous work, Dr Bhatia created nanoparticles that can detect the activity of enzymes called 'proteases' - which help cancer cells escape their original locations or settle in new ones.
These nanoparticles are coated with peptides that are split by different proteases and, once released into the bloodstream, these peptides can then be concentrated and more easily detected in a urine sample.
The original peptide biomarkers were designed to be detected based on small variations in their masses, using a mass spectrometer - but this kind of equipment is likely not to be available in lower-resource settings.
So researchers instead developed sensors that can be analysed more easily and affordably using DNA barcodes read using a specially designed technology called 'CRISPR'.
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The research team additionally had to use a chemical modification to protect the circulating DNA reporter barcodes from being broken down whilst travelling in the blood.
Each DNA barcode is attached to a nanoparticle by a linker that can be severed by a specific protease. If that protease is present, the DNA molecule is released and free to circulate, eventually ending up in the urine.
Once the sensors are secreted in the urine, the sample can be analysed using a paper strip that recognizes a reporter activated by a CRISPR enzyme. When a particular DNA barcode is present in the sample, Cas12a amplifies the signal so that it is seen as a dark strip on a paper test.
The particles can be designed to carry many different DNA barcodes, each of which detects a different type of protease activity, which allows for 'multiplexed' sensing. Using a larger number of sensors provides a boost in both sensitivity and specificity, allowing the test to more easily distinguish between tumour types.
In recent tests with mice, the researchers demonstrated a panel of five DNA barcodes could accurately distinguish tumours that first arose in the lungs from those formed by colorectal cancer cells that had metastasised to the lungs.
Liangliang Hao, a former MIT research scientist who is now an assistant professor of biomedical engineering at Boston University and lead author of the study, explained: "Our goal here is to build up disease signatures and to see whether we can use these barcoded panels not only to read out a disease but also to classify a disease or distinguish different cancer types."
For future human use, the researchers expect that they may need to use more than five barcodes as they did in the mice, due to the variety in patients' tumours.
Toward this end, the researchers teamed up with scientists at the Broad Institute of MIT and Harvard to create a microfluidic chip that can be used to read up to 46 different barcodes from just one sample.
This kind of testing could be used not only for detecting cancer but also for measuring how well a patient’s tumour responds to treatment and whether it has recurred after treatment. The researchers are now working on further developing the particles with the goal of testing them in humans.
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