(1363-D) quantum-based sensing of microRNA biomarkers of breast cancer using NV-center nanodiamonds.
Tuesday, February 6, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: Cancer screening has the primary goal of reducing the death rate from this disease by detecting cancer before symptoms appear. This allows treatment when the cancer is most curable. Our broad, long-term goal is to develop quantum-based sensing technology for screening biomarkers of breast cancer, such as microRNAs. The quantum sensor used in this work is the nitrogen-vacancy (NV) center, a photoluminescent impurity in a diamond lattice with unique optical and spin properties, at room-temperature.
MicroRNAs (miRNAs) are a large class of non-coding RNAs, approximately 22 nucleotides in length, that are involved in the post-transcriptional silencing of messenger RNAs (mRNAs). MiRNAs bind to the mRNA 3-prime untranslated region, which results in mRNA cleavage, degradation, or translational repression. Aberrant expression of miRNAs is associated with the onset and progression of breast cancer and can have different roles in cancer. These can be described as oncogenic or tumor-suppressive with upregulation of oncogenic microRNAs leading to inhibited expression of tumor-suppressive genes, while downregulation of tumor-suppressive microRNAs can increase signaling pathways that enhance tumor development. MiRNAs have properties that make them good diagnostic biomarkers for liquid biopsy (LB), as they remain stable even under severe conditions such as pH variations or multiple freeze–thaw cycles. Additionally, they are found in different body fluids, either free, bound to proteins, or encapsulated in exosomes, and this facilitates their extraction and analysis. However, miRNAs are a challenging target to detect by conventional RT-qPCR, due to their small size, low abundance, and sequence homology among family members. There are also methodological challenges and quantification issues to overcome before miRNAs become clinically valid biomarkers. Despite these concerns there remains considerable interest in the use of miRNAs as an analytical tool in clinical practice.
We used NV-center nanodiamonds to evaluate if a quantum-based sensing technology called diamond magnetometry (DM), could detect microRNA biomarkers of inflammatory breast cancer. We converted NV-center nanodiamonds into novel quantum sensors specific for microRNA (miR) targets and then evaluated their sensing ability using an all-optical technique called optically detected magnetic resonance (ODMR). Using purified miR RNA oligonucleotides, we demonstrated that DM could detect microRNAs with remarkable sensitivity and specificity.
DM does not require nucleic acid amplification or costly reagents. It is simple, inexpensive, fast, and, in initial studies, we have demonstrated sensitivity in the low picomolar range although the true limit of detection of DM is expected to be in the attomolar range. The use of DM in basic research will help in understanding the role of microRNAs in cancer cells and in clinical settings, can be used for early breast cancer screening assays using liquid biopsies. Future work will explore the use of DM for cancer treatment monitoring, and post-treatment follow-up.