Early cancer detection is an all-too-familiar challenge for oncologists who routinely discover tumors after they have progressed to dangerous and life-threatening stages. While some semi-frequent checks such as endoscopies and mammograms are recommended for particular age groups, the field still lacks a viable method to frequently screen for cancer without significant cost to the healthcare system and a risk to patient health. A recent report by Dr. Daniel Heller’s team at Memorial Sloan Kettering Cancer Center (MSKCC) describes a new nanosensor technology that promises to bring accessible and continuous monitoring to enable detection of cancer at its earliest stages.
Schematic of carbon nanotube optical sensor for early disease detection via biomarker recognition. Image courtesy of Heller Lab
A significant research effort has been put into identifying molecular biomarkers that would signal underlying diseases such as cancer. A subset of these molecules, miRNAs, are easily found in accessible bodily fluids, such as blood or urine. However, detecting them is labor- and resource-intensive. To address this, the team used carbon nanotubes to design a miniature sensor. They took advantage of the intrinsic ability of carbon nanotubes to fluoresce in the near-infrared range, the light being suitable for harmless transmission through soft body tissue. The intensity and wavelength of this fluorescence is highly sensitive to the surface condition of the nanotubes.
Pairing the nanotubes with specific oligonucleotide sequences allowed the researchers to fish out target miRNAs from relevant biofluids, while maintaining the ability to detect a variety of targets by changing the detection sequence. Upon hybridization to the target miRNA, the detection oligonucleotide is displaced from the nanotube’s surface and replaced by surfactant molecules. This process alters the nanotube’s surface chemistry, allowing for measurable shift in its fluorescence signal that correlates with the amount of miRNA present in the nanosensor’s environment.
The researchers showed that this technology reliably detected clinically relevant miRNA biomarkers in serum and urine samples. They also embedded the nanosensor in a semi-permeable membrane that was implanted into a live mouse, demonstrating its functionality and that the signal was detectable through tissue. They even showed that altering the chemistry of the nanotubes enabled for multiplexed detection of two target biomarkers at different wavelengths.
While a lot of optimization and safety demonstrations need to be completed before this technology makes it to the clinic, it would certainly be more accessible than the standard biopsy or imaging test. This platform opens the door for continuous monitoring of biomarkers, making it as easy as shining an infrared light and reading the output – just like a barcode. Immediate applications include monitoring the progress of a therapy, and for detecting tumor growths in high-risk individuals such as survivors of cancers with high recurrence rates. The team envisions that such implantable sensors can be coupled with wearable technology to allow for continuous monitoring and fingerprinting of disease-associated biomarkers, seamlessly conveying this information to a physician.
Article in Nature Biomedical Engineering: A carbon nanotube reporter of microRNA hybridization events in vivo
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