Early cancer detection is critical for improving patient outcomes, and MIT engineers have achieved a significant breakthrough in this area. They have developed an innovative nanoparticle sensor technology that promises to simplify cancer diagnosis through a non-invasive urine test. This advancement, detailed in a compelling Diagnosis Paper, could transform how cancer is detected, classified, and monitored, offering a more accessible and affordable approach for patients worldwide.
These novel sensors are engineered to identify a wide array of cancerous proteins, providing not only early detection but also the potential to differentiate tumor types and assess treatment response. The core mechanism involves nanoparticles designed to interact with tumors, triggering the release of short DNA sequences, or “barcodes,” that are subsequently excreted in urine. Analyzing these DNA barcodes in what could be termed a diagnosis paper format provides a unique molecular fingerprint of the patient’s tumor.
The researchers have ingeniously designed this diagnostic approach to be user-friendly, envisioning a paper strip test, much like current at-home COVID-19 tests. This format is central to their goal of creating a readily deployable diagnosis paper system, making cancer diagnostics more accessible and affordable, particularly in resource-limited settings.
Professor Sangeeta Bhatia from MIT, a leading figure in this research, emphasizes the democratizing potential of this technology. “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,” she explains. This vision of a point-of-care diagnosis paper aligns with the growing need for accessible healthcare solutions.
Preclinical studies in mice have demonstrated the efficacy of these sensors in detecting the activity of five distinct tumor-associated enzymes. Furthermore, the researchers successfully scaled up their method to distinguish at least 46 different DNA barcodes within a single sample using microfluidic analysis. This multiplexing capability, crucial for a comprehensive diagnosis paper, enhances both the sensitivity and specificity of the test.
This groundbreaking research, with Bhatia as the senior author and Liangliang Hao as the lead author, is published in Nature Nanotechnology, solidifying its credibility as a significant diagnosis paper in the field of medical technology.
Unlocking Disease Signatures with DNA Barcodes in Diagnosis Papers
The foundation of this innovative diagnostic approach lies in the concept of “synthetic biomarkers.” For years, Dr. Bhatia’s lab has pioneered the development of these biomarkers to overcome the limitations of naturally occurring cancer biomarkers, which are often scarce, especially in early-stage disease. Synthetic biomarkers, as detailed in their diagnosis paper, amplify subtle changes within tumors, making early detection more feasible.
Building on previous work with nanoparticles that detect protease activity, enzymes crucial for cancer metastasis, this new technology utilizes DNA barcodes for signal amplification and simplified detection. The nanoparticles are coated with peptides sensitive to different proteases. Upon encountering tumor-associated proteases, these peptides are cleaved, releasing the attached DNA barcodes into circulation, eventually concentrating in the urine.
The initial peptide-based biomarkers relied on mass spectrometry for detection, a technique not always accessible in resource-constrained environments. This motivated the shift towards DNA barcodes and CRISPR technology, enabling a more affordable and user-friendly analysis method, perfectly suited for a diagnosis paper format.
A key innovation was the incorporation of phosphorothioate modification to protect the DNA barcodes from degradation in the bloodstream. This stabilization technique, also used in modern RNA vaccines, ensures the barcodes’ integrity until they reach the urine for analysis, a crucial aspect highlighted in the diagnosis paper.
Two types of nanoparticles were employed in this study: polymer-based particles, already FDA-approved for human use, and nanobodies, antibody fragments designed to target tumor sites. Both types effectively deliver and release the DNA barcodes upon protease activation, contributing to the robust nature of this diagnosis paper methodology.
The analysis of urine samples is performed using a paper strip that reacts to a reporter activated by the CRISPR enzyme Cas12a. The presence of specific DNA barcodes triggers Cas12a, amplifying the signal and producing a visible dark strip on the paper, thus creating a tangible output for the diagnosis paper.
The ability to equip nanoparticles with multiple DNA barcodes, each specific to a different protease, allows for multiplexed sensing. This capability, thoroughly explored in their diagnosis paper, significantly enhances the test’s sensitivity and specificity, enabling better discrimination between different tumor types and disease states.
From Mice to Humans: The Future of Cancer Diagnosis Papers
In vivo studies in mice, as documented in their diagnosis paper, demonstrated the capability of a five-DNA barcode panel to accurately distinguish between primary lung tumors and lung metastases from colorectal cancer. This success underscores the potential of this technology to develop comprehensive “disease signatures.”
“Our goal here is to build up disease signatures and to see whether we can use these barcoded panels not only read out a disease but also to classify a disease or distinguish different cancer types,” Hao explains. This aspiration to create detailed disease profiles is central to the future applications of this diagnosis paper technology.
Recognizing the complexity of human tumors, the researchers anticipate the need for a larger panel of barcodes for human applications. To address this, they collaborated with experts at the Broad Institute to develop a microfluidic chip capable of analyzing up to 46 different DNA barcodes from a single sample. This advancement is crucial for translating the diagnosis paper from research to clinical practice.
Beyond early detection, this technology holds promise for monitoring treatment response and detecting cancer recurrence. Glympse Bio, a company co-founded by Professor Bhatia, has already completed phase 1 clinical trials for an earlier version of these urinary diagnostic particles, demonstrating their safety in humans. These trials pave the way for future human testing of this innovative diagnosis paper approach.
The research team, including co-authors Hao, Zhao, Welch, and others, is actively working to further develop these particles, aiming to bring this groundbreaking diagnosis paper technology closer to clinical reality and revolutionize cancer diagnostics for patients worldwide.
References:
- Hao, L., Zhao, R.T., Welch, N.L. et al. Paper-based multiplexed urine test for cancer diagnosis using DNA-barcoded nanoprobes. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01372-9
- MIT News Office. “Noninvasive diagnostics for cancer.” MIT News, 16 Dec. 2012, https://news.mit.edu/2012/noninvasive-diagnostics-for-cancer-1216
