It is well known that cancer diagnosis in early stages can greatly increase survival rates and decrease treatment cost. Diagnostics such as colonoscopies and mammograms are among the best tools in the fight against colon and breast cancers since they allow for routine screening and therefore early detection. Early detection of lung cancer is particularly problematic-there are no routine screens. As a result, lung cancer is the most common of all cancer deaths; annually causing 160,000 deaths in the United States and 1.2 million worldwide. Routine screening of biomarkers is possible with simple, low cost, non-invasive assays making them a promising approach for early cancer detection; they have already been used to great effect for prostate cancer and breast cancer, leading to their almost 100% survival rates when detected early. MicroRNAs are a powerful class of biomarkers for a wide range of diseases including heart disease, sepsis, and all types of cancer, including indication of metastasis and progression stage. A miRNA diagnostic platform could be used to test for several cancers simultaneously, essentially allowing for routine early detection and identification of all cancers from a small blood sample drawn at an annual physical exam. Unfortunately, current methods of miRNA detection suffer from a variety of shortcomings including speed, amplification errors, and cost, limiting their role in routine cancer diagnosis. Nanopore detection of miRNA has the potential to address these shortcomings, combining the low-cost features of microarray assays with qRT-PCR's ability to quantify the amount of miRNA present, but with low cost instrumentation and no amplification. Nanopore miRNA detection works by detecting the binding of target miRNAs to probes which are then measured electrically using a nanopore. The general idea of this method is similar to optical bar coding technologies but utilizes low cost electronics and simplified probes. This method has already successfully shown detection of circulating miRNAs in cancer patients. Librede is developing a nanopore-based microRNA instrumentation and assays that will enable routine low cost cancer screening.
We aim to develop an automated instrument based on our established artificial membrane platform combined with nanopore technology for the cancer diagnostic market. In the work proposed here, we will automate our nanopore platform to detect lung cancer-related miRNA, quantitatively determine miRNA concentrations, and measure miRNA from blood samples. This will lead to a laboratory prototype that will be used in Phase II to measure miRNA in clinical samples. Successful completion of this work will lead to a new tool for early and routine detection and diagnosis of cancer.

Public Health Relevance

Cancer survivability is greatly improved by early detection, which is most easily achieved if it is convenient, routine, low cost, and non-invasive. Librede has successfully used nanopores to detect miRNA cancer biomarkers, which can indicate the presence and progression of many different cancer types. We propose here to establish the feasibility for an automated parallel instrument for nanopore-based microRNA detection.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA196132-01
Application #
8904432
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rahbar, Amir M
Project Start
2015-05-01
Project End
2015-10-31
Budget Start
2015-05-01
Budget End
2015-10-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Librede, Inc.
Department
Type
DUNS #
828873021
City
Sherman Oaks
State
CA
Country
United States
Zip Code
91403